Announcement TypeThis
is a reissue of PAR-06-451, which was
previously released June 9, 2006.

Update: The following update relating to this announacement has been issued:

August 16, 2010 - IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond. As of January 25, all corrections must be complete by the due date for an application to be considered on-time.
See NOT-OD-10-123.

December 30, 2009 -
This FOA has been updated to reflect the new requirements from NIH’s Enhancing Peer Review Initiative. The new requirements are effective for submissions intended for due dates January 25, 2010 and beyond. If submitting an application intended for a due date of January 25, 2010 and beyond, follow the guidance below and be sure to use the Adobe-Forms-B version of the application forms and instructions. If applying for a due date before January 25, 2010, follow the guidance in the archived version of this FOA and be sure to use the Adobe-Forms-A version of the application forms and instructions.

NOTICE: Applications submitted in response to this FOA for Federal
assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424
Research and Related (R&R) forms and the SF424 (R&R) Application
Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application
guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter
called Grants.gov/Apply).

A registration process is necessary before submission and
applicants are highly encouraged to start the process at least 4 weeks prior to
the grant submission date. See Section IV.

Key Dates
Release/Posted Date: November
19, 2007
Opening Date: February 7, 2008 (Earliest
date an application may be submitted to Grants.gov)Letters of Intent Receipt Date(s):A letter of intent is not required for the funding
opportunity.NOTE: On-time submission
requires that applications be successfully submitted to Grants.gov no later
than 5:00 p.m. local time (of the applicant institution/organization).Application Submission/Receipt Date(s): March 7, 2008; July 9, 2008; November 7, 2008; March 9, 2009; July 9, 2009;
November 9, 2009; March 9, 2010; July 9, 2010; November 9, 2010.Application Review Date(s): June/July 2008; October/November
2008; February/March 2009; June/July 2009; October/November 2009; February/March
2010; June/July 2010; October/November 2010; February/March 2011.Council Meeting Date(s): October 2008; January
2009; May 2009; October 2009; January 2010; May 2010; October 2010; January
2011; May 2011.Earliest Start Date(s): December 2008; April 2009;
July 2009; December 2009; April 2010; July 2010; December 2010, April 2011;
July 2011.Expiration Date: November 10, 2010

Due Dates for E.O. 12372

Not
Applicable.

Additional
Overview Content

Executive Summary

Purpose. This FOA is intended to promote translational research in
new agent/modality development with timely exploitation of new cancer-relevant
therapeutic and/or preventive strategies that involve
defined molecular targets. Applications are solicited for pilot clinical
trials exploring individual anticancer agents/modalities and/or their
combinations in the context of specific molecular targets. Applicants may propose Phase 0, Phase I, Phase II, and/or other
pilot cancer clinical trials. In addition, patient monitoring and laboratory
correlative studies related to clinical trials may be proposed. Applications that explore
complementary and alternative approaches for cancer prevention and/or treatment
are also encouraged. Clinical trials
proposed may be oriented on AIDS-associated malignancies and cancer-related
nutritional interventions. Applicants must include the clinical protocol
within the Appendix to ensure proper accelerated peer
review with the goal of issuing new awards within 6 months of receipt of the
grant application.

Mechanism
of Support.This FOA will use
the NIH exploratory/developmental (R21) grant mechanism for exploratory, pilot
projects. Applicants planning to propose fully
developed research projects supported by preliminary data should consider a
related FOA (PA-07-356) that
solicits applications for clinical therapeutic and
preventive trials under the NIH research project (R01) grant mechanism.

Funds Available
and Anticipated number of Awards: Awards issued under this FOA are contingent upon the
availability of funds and the submission of a sufficient number of meritorious
applications; therefore, the anticipated number of awards is not known.

Applications that do
not propose a cancer clinical trial or patient monitoring or laboratory studies
linked to a cancer clinical trial may be returned to applicants without being
reviewed.

Budget and Project Period: The total project period
for an application submitted in response to this funding opportunity may not
exceed 2 years. Direct costs are limited to $500,000 over an R21 2-year
period, with no more than $250,000 in direct costs allowed in any single year.

Eligible Project
Directors/Principal Investigators (PDs/PIs): Individuals with the skills, knowledge,
and resources necessary to carry out the proposed research are invited to work
with their institution to develop an application for support. Individuals from
underrepresented racial and ethnic groups as well as individuals with
disabilities are always encouraged to apply for NIH support.

Renewals. R21 awards are
not renewable.

Resubmissions. Applicants may submit a resubmission, but such
applications must include an Introduction addressing the issues raised in
the previous critique (Summary Statement).

Application and Submission
Information:Applicants
may submit more than one application, provided each application is
scientifically distinct.

Application
Materials. See Section IV.1 for application materials. General
Information. For general information on SF424 (R&R) Application and
Electronic Submission, see these Web sites:

The major purpose of this funding opportunity announcement
(FOA) is to expedite clinical translation of basic research discoveries in
cancer biology, through the development of novel
anti-cancer drugs, diagnostic tools, treatments, and preventions.

BACKGROUND

Recent advances in our understanding of the basic biology
and genetics of cancer, as well as the development of microarray technologies,
proteomics, and bioinformatics, have allowed the
identification of several new molecular targets and signaling pathways in
cancer cells. Therefore, these discoveries in cancer research have presented
excellent translational opportunities for development of new drugs and their initiation into clinical studies.

Novel agents that suppress tumor growth exert their actions
through multiple mechanisms. These actions include: control of cell cycle;
activation of tumor suppressor genes; increase in tumor cell apoptosis; inhibition of tumor DNA repair processes; tumor
vaccines/immune stimulatory agents; blockage of specific signaling pathways
(e.g., inhibitors for kinases, phosphatases, and RNA-interference-mediated
downregulation); and alterations in the tumor microenvironment, such as inhibition of angiogenesis and improved
methods of drug delivery (e.g., nanoparticle drug carriers). Combined with new
diagnostic assays and tools, several of these potential anti-metastatic
treatment modalities are ready to be tested for clinical
efficacy.

This FOA is intended to stimulate clinical translational
research and accelerate the process of targeted cancer drug development,
treatment, and prevention. In addition, applications that explore
complementary and alternative approaches for cancer
prevention and treatment are also encouraged.

SCOPE

This FOA will expand upon various modalities that are
currently used for the treatment of early and advanced cancers, which include
either chemo-, thermo- and cryo-therapies, biologic agents, radiation, and/or surgery. Therefore, this FOA will
continue to support scientific, technological, clinical, and logistical needs
in novel cancer treatments and diagnoses.

Clinical studies that evaluate the effect(s) of novel
nutritional interventions, such as herbal therapies,
dietary supplements, and bioactive food components aimed at reducing cancer
treatment-related side effects and toxicities, are solicited. Clinical studies
that propose improvements and evaluations of single agent or combinatorial treatments, treatment-associated morbidities, and patients
prognoses are also encouraged to apply. Finally, investigators who propose to
conduct clinical studies of unconventional pharmacological and biological
interventions (e.g., antineoplastons, Coley's toxin,
enzyme therapies, etc.) are invited to apply.

This FOA will complement the Rapid Access to Intervention
Development (RAID) program (http://dtp.nci.nih.gov/docs/raid/raid_index.html) by providing initiatives coupled with accelerated peer
review and funding. These measures will support both the clinical and
laboratory costs associated with early clinical testing to ensure the timely
development of new therapeutic and preventive approaches.

Features of this program include a modular budget,
inclusion of the clinical protocol within the grant application, and
accelerated peer review with the goal of issuing new awards within 6 months of
receipt of the application. Inclusion of the complete
clinical protocol within the human subjects section of the application will
ensure proper peer review of the application as well as the protocol. Other
key features include no prerequisite for extensive preliminary data in the
grant application, support for exploratory
translational research studies, and rapid development and application of novel
clinical cancer therapies. Investigators may apply for a maximum of 2 years of
funding support using the NIH exploratory/developmental (R21) grant mechanism for up to $250,000 direct costs per year.

The evolution and vitality of the biomedical sciences
require a constant infusion of new ideas, techniques, and points of view.
These may differ substantially from current thinking or practice and may not
yet be supported by substantial preliminary
data. Through use of the R21 mechanism, the NIH seeks to foster the
introduction of novel scientific ideas, model systems, tools, agents, targets,
and technologies that have the potential to substantially advance biomedical research.

The R21 mechanism is intended to encourage new exploratory
and developmental research projects. For example, such projects could
assess the feasibility of a novel area of investigation or a new experimental
system that has the potential to enhance
health-related research. Another example could include the unique and
innovative use of an existing methodology to explore a new scientific
area. These studies may involve considerable risk but may lead to a
breakthrough in a particular area, or to the
development of novel techniques, agents, methodologies, models, and/or
applications that could have a major impact on a field of biomedical,
behavioral, and/or clinical research.

Applications for R21 awards should describe projects
distinct from those supported through the traditional
R01 mechanism. For example, long-term projects, or projects designed to
increase knowledge in a well-established area, will not be considered for R21
awards. Applications submitted under this mechanism should be exploratory and novel. These studies should break new ground
or extend previous discoveries toward new directions or applications.

This FOA will use the NIH
Exploratory/Developmental Research Grant (R21) award
mechanism. As an applicant, you will be solely
responsible for planning, directing, and executing the proposed project.

This FOA uses Just-in-Time information concepts. It also uses the modular
as well as the non-modular budget formats (see the Modular Applications and
Awards section of the NIH
Grants Policy Statement. Specifically, if you are submitting an
application with direct costs in each year of $250,000 or less (excluding
consortium Facilities and Administrative [F&A] costs), use the PHS398
Modular Budget component provided in the SF424 (R&R) Application Package
and SF424 (R&R) Application Guide (see specifically Section 3.4, Modular
Budget Component, of the Application Guide).

Foreign applicants must complete and submit budget requests using the
Research & Related Budget component found in the application package for
this FOA. See NOT-OD-06-096,
August 23, 2006.

Exploratory/developmental grant support is for new
projects only; competing renewal (formerly competing continuation)
applications will not be accepted. Applicants may submit a resubmission, but
such applications must include an Introduction addressing issues raised in
the previous critique (Summary Statement).

2. Funds Available

Because the nature and scope of the proposed research will vary from
application to application, it is anticipated that the size and duration of
each award will also vary. Although the financial plans of the Institutes and
Centers (ICs) provide support for this program, awards pursuant to this funding
opportunity are contingent upon the availability of funds and the submission of
a sufficient number of meritorious applications.

The
total project period for an application submitted in response to this funding
opportunity may not exceed 2 years. Although the size of award may vary with
the scope of research proposed, it is expected that applications will stay within the budgetary guidelines for an
exploratory/developmental project; direct costs are limited to $500,000 over an R21 2-year
period, with no more than $250,000 in direct costs allowed in any single year.
Applicants may request direct costs in $25,000
modules, up to the total direct costs limitation of $500,000 for the combined
2-year award period. NIH grants policies as
described in the NOT-OD-05-004, November 2, 2004.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit an application(s) if your
institution/organization has any of the following characteristics:

Any individual with the skills, knowledge, and resources necessary to
carry out the proposed research as the Project Director/Principal Investigator
(PD/PI) is invited to work with his/her organization to develop an application
for support. Individuals from underrepresented racial and ethnic groups as
well as individuals with disabilities are always encouraged to apply for NIH
support.

More than one PD/PI, or multiple PDs/PIs, may be designated on the
application for projects that require a team science approach that clearly
does not fit the single-PD/PI model. Additional information on the
implementation plans and policies and procedures to formally allow more than
one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All
PDs/PIs must be registered in the NIH eRA Commons prior to the submission of
the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a single PD/PI or multiple PD/PI
grant is the responsibility of the investigators and applicant organizations
and should be determined by the scientific goals of the project. Applications
for multiple PD/PI grants will require additional information, as outlined in
the instructions below.

When considering multiple PDs/PIs, please be aware that the structure
and governance of the PD/PI leadership team as well as the knowledge, skills,
and experience of the individual PD/PIs will be factored into the assessment of
the overall scientific merit of the application. Multiple PDs/PIs on a
project share the authority and responsibility for leading and directing the
project, intellectually and logistically. Each PD/PI is responsible and
accountable to the grantee organization, or, as appropriate, to a collaborating
organization, for the proper conduct of the project or program, including the
submission of required reports. For further information on multiple PDs/PIs,
please see http://grants.nih.gov/grants/multi_pi.

Applicants may submit more than one application, provided
each application is scientifically distinct.

Section IV. Application and Submission Information

Registration:
Appropriate registrations with Grants.gov and eRA Commons must be completed on or before the due date in order to successfully submit an application. Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered with both Grants.gov and the Commons. All registrations must be complete by the submission deadline for the application to be considered on-time (see 3.C.1 for more information about on-time submission).

To download a SF424 (R&R) Application Package and
SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for
this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

The individual(s)
designated as PDs/PIs on the application must also be registered in the
NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs must
be registered and be assigned the PI role in the eRA Commons prior
to the submission of the application.

Each PD/PI must hold a
PD/PI account in the Commons. Applicants should not share a Commons
account for both an Authorized Organization Representative/Signing
Official (AOR/SO) role and a PD/PI role; however, if they have both a
PD/PI role and an Internet Assisted Review (IAR) role, both roles should
exist under one Commons account.

When multiple PDs/PIs are
proposed, all PDs/PIs at the applicant organization must be affiliated
with that organization.PDs/PIs located at another institution need
not be affiliated with the applicant organization, but must be affiliated
with their own organization to be able to access the Commons.

This
registration/affiliation must be done by the AOR/SO or their designee who
is already registered in the Commons.

Both the PD/PI(s) and
AOR/SO need separate accounts in the NIH eRA Commons since both are
authorized to view the application image.

Several of the steps of the registration process could
take 4 weeks or more. Therefore, applicants should immediately check with
their business official to determine whether their organization/institution is
already registered in both Grants.gov and
the Commons. The NIH will
accept electronic applications only from organizations that have completed all
necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R)
application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package
directly attached to a specific FOA can be used. You will not be able to use
any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA),
although some of the "Attachment" files may be useable for more than
one FOA.

Prepare all applications using the SF424 (R&R)
application forms and in accordance with the SF424
(R&R) Application Guide (MS
Word or PDF).

The SF424 (R&R) Application Guide is
critical to submitting a complete and accurate application to NIH. There are
fields within the SF424 (R&R) application components that, although not
marked as mandatory, are required by NIH (e.g., the Credential log-in field
of the Research & Related Senior/Key Person Profile component must contain
the PD/PIs assigned eRA Commons User ID). Agency-specific instructions for
such fields are clearly identified in the Application Guide. For additional
information, see Frequently Asked Questions Application Guide,Electronic Submission
of Grant Applications.

The SF424 (R&R) application is comprised of data
arranged in separate components. Some components are required, others are
optional. The forms package associated with this FOA in Grants.gov/APPLYwill include all
applicable components, required and optional. A completed application in
response to this FOA will include the following components:

Prepare detailed budgets for all applications (that is,
complete the Research & Related Budget component of the SF424
(R&R) application forms not the PHS398 Modular Budget component).
See NOT-OD-06-096.

Charge
back of customs and import fees is not allowed.

U.S. Government grants cannot pay
taxes in foreign countries, including VAT tax.

Format:
Every effort should be made to comply with the format specifications,
which are based upon a standard U.S. paper size of 8.5 x 11 within each
PDF.

Funds
for up to 8% administrative costs (excluding equipment) may be requested.
See NOT-OD-01-028,
March 29, 2001.

Organizations
must comply with Federal/NIH policies on human subjects, animals, and
biohazards.

Organizations
must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., Administrative and National Policy
Requirements.

Proposed
research should provide special opportunities for furthering research programs
through the use of unusual talent, resources, populations, or environmental
conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be
designated as the "Contact PI, who will be responsible for all
communication between the PDs/PIs and the NIH, for assembling the application
materials outlined below, and for coordinating progress reports for the
project. The contact PD/PI must meet all eligibility requirements for PD/PI
status in the same way as other PDs/PIs, but has no other special roles or
responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in Item 13 of the
SF424 (R&R) Cover component. All other PDs/PIs should be listed in
the Research & Related Senior/Key Person component and assigned the project
role of PD/PI. Please remember that all PDs/PIs must be registered in
the eRA Commons prior to application submission. The Commons ID of
each PD/PI must be included in the Credential field of the Research &
Related Senior/Key Person component. Failure to include this data field
will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a
new section describing the leadership of the project.

Multiple PD/PI Leadership Plan: For applications designating multiple
PDs/PIs, a new section of the research plan, entitled Multiple PD/PI
Leadership Plan, must be included. A rationale for choosing a multiple PD/PI
approach should be described. The governance and organizational structure
of the leadership team and the research project should be described, including
communication plans, process for making decisions on scientific direction, and
procedures for resolving conflicts. The roles and administrative,
technical, and scientific responsibilities for the project or program should be
delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to
specific components of the project or the individual PDs/PIs should be
delineated in the Leadership Plan. In the event of an award, the
requested allocations may be reflected in a footnote on the Notice of Award
(NoA).

Applications Involving Multiple Institutions

When multiple institutions are involved, one institution must be
designated as the prime institution and funding for the other institution(s)
must be requested via a subcontract to be administered by the prime
institution. When submitting a detailed budget, the prime institution should
submit its budget using the Research & Related Budget component. All
other institutions should have their individual budgets attached separately to
the Research & Related Subaward Budget Attachment(s) Form. See
Section 4.8 of the SF424 (R&R) Application Guide for further instruction
regarding the use of the subaward budget form.

When submitting a modular budget, the prime institution completes the
PHS398 Modular Budget component only. Information concerning the
consortium/subcontract budget is provided in the budget justification.
Separate budgets for each consortium/subcontract grantee are not required when
using the Modular budget format. See Section 3.4 of the Application Guide for
further instruction regarding the use of the PHS398 Modular Budget component.

To submit an application in response to this FOA, applicants should access this
FOA via http://www.grants.gov/Apply and follow Steps 1-4. Note: Applications must only be submitted electronically.
PAPER APPLICATIONS WILL NOT BE ACCEPTED.3.C. Application
Processing

3.C.1 Submitting On-Time

Applications may be submitted on or after the opening date and must be successfully
received by Grants.gov no later than 5:00 p.m. local
time(of the applicant
institution/organization) on the application due date(s). (See Section
IV.3.A. for
all dates.) If
an application is not submitted by the due date(s) and time, the application
may be delayed in the review process or not reviewed. All applications must meet the following criteria to be considered on-time:

All registrations must be complete prior to the submission deadline

The application must receive a Grants.gov tracking number and timestamp (or eRA help desk ticket confirming a system issue preventing submission) by 5:00 p.m. local time on the submission deadline date.

Any system identified errors/warnings must be corrected and the submission process completed within the error correction window.

Submission to Grants.gov is not the last step - applicants must follow their application through to the eRA Commons to check for errors and warnings and view their assembled application!

3.C.2 Two Day Window to Correct eRA Identified Errors/Warnings

IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond.
As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See
NOT-OD-10-123.

Once an application
package has been successfully submitted through Grants.gov NIH provides applicants a two day error correction window to correct any eRA identified errors or warnings before a final assembled application is created in the eRA Commons. The standard error correction window is two (2) business days, beginning the day after the submission deadline and excluding weekends and standard federal holidays. All errors must be corrected to successfully complete the submission process. Warnings will not prevent the application from completing the submission process.

Note that the following caveats apply:

Initial application submission must be on-time.

The AOR/institutions is expected to enforce that application changes made within the error correction window are restricted to those necessary to address system-identified errors/warnings. NIH may reject any application that includes additional changes.

Proof of on-time submission (e.g., Grants.gov timestamp and tracking number) and description of all changes made within the window must be documented in the PHS 398 Cover Letter component of the application.

3.C.3 Viewing an Application in the eRA Commons

Once any eRA identified errors have been addressed and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday Friday, excluding Federal holidays) to view the assembled application before it automatically moves forward to NIH for further processing.

If
everything is acceptable, no further action is necessary. The application will
automatically move forward for processing by the Division of Receipt and
Referral, Center for Scientific Review, NIH, after two business days, excluding
Federal holidays.

Prior
to the submission deadline, the AOR/SO can Reject the assembled application
and submit a changed/corrected application within the two-day viewing window.
This option should be used if the AOR/SO determines that warnings should be
addressed or if information was lost or compromised during transmission.
Reminder: warnings do not stop further application processing. If an
application submission results in warnings (but no errors), it will
automatically move forward after two business days if no action is taken.
Please remember that some warnings may not be applicable or may need to be
addressed after application submission.

If
the two-day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.gov
system issue, the application does not correctly reflect the submitted
application package (e.g., some part of the application was lost or did not
transfer correctly during the submission process). The AOR/SO should first
contact the eRA Commons Helpdesk to confirm the system error,
document the issue, and determine the best course of action. NIH will not
penalize the applicant for an eRA Commons or Grants.gov system issue.

If
the AOR/SO chooses to Reject the image after the submission deadline for a
reason other than an eRA Commons or Grants.gov system failure, a
changed/corrected application still can be submitted, but it will be subject to
the NIH late policy guidelines and may not be accepted. The reason for
this delay should be explained in the cover letter attachment.

Both
the AOR/SO and PD/PI will receive e-mail notifications when the application is
rejected or the application automatically moves forward in the process after
two days.

Upon receipt, applications will
be evaluated for completeness by the Center for Scientific Review (CSR), NIH.
Incomplete applications will not be reviewed.

All NIH awards are subject to the
terms and conditions, cost principles, and other considerations described in
the NIH
Grants Policy Statement.

Pre-award costs are allowable. A
grantee may, at its own risk and without NIH prior approval, incur obligations
and expenditures to cover costs up to 90 days before the beginning date of the
initial budget period of a new award if such costs: are necessary to conduct
the project, and would be allowable under the grant, if awarded, without NIH
prior approval. If specific expenditures would otherwise require prior
approval, the grantee must obtain NIH approval before incurring the cost. NIH
prior approval is required for any costs to be incurred more than 90 days
before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a
competing or non-competing award imposes no obligation on NIH either to make
the award or to increase the amount of the approved budget if an award is made
for less than the amount anticipated and is inadequate to cover the pre-award
costs incurred. NIH expects the grantee to be fully aware that pre-award costs
result in borrowing against future support and that such borrowing must not
impair the grantee's ability to accomplish the project objectives in the
approved time frame or in any way adversely affect the conduct of the project.
See the NIH
Grants Policy Statement.

6. Other
Submission Requirements

PD/PI
Credential (e.g., Agency Login)

The NIH requires the PD/PI to
fill in his/her Commons User ID in the PROFILE Project Director/Principal
Investigator section, Credential log-in field of the Research & Related
Senior/Key Person Profile component. The applicant organization must include
its DUNS number in its Organization Profile in the eRA Commons. This DUNS
number must match the DUNS number provided at CCR registration with
Grants.gov. For additional information, see Registration FAQs Important
Tips -- Electronic
Submission of Grant Applications.

Organizational DUNS

The applicant organization must
include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with
Grants.gov. For additional information, see Frequently Asked Questions
Application Guide, Electronic
Submission of Grant Applications.

Warning: Please be sure that you observe the direct
cost, project period, and page number limitations specified below for this
FOA. Application processing may be delayed or the application may be rejected
if it does not comply with these requirements.

PHS398 Research Plan Component Sections

All application instructions outlined in the SF424
(R&R) Application Guide (MS
Word or PDF) are to be followed, incorporating "Just-in-Time" information
concepts, and with the following requirements for R21 applications:

R21 applications will use the modular as well as the
non-modular budget format and "Just-in-Time" information concepts,
with direct costs requested in $25,000 modules, up to the total direct costs
limitation of $500,000 over an R21 2-year period. No more than $250,000 in
direct costs will be allowed in any single year. All foreign applicants must complete and submit budget
requests using the Research & Related Budget component found in the
application package for this FOA. See NOT-OD-06-096,
August 23, 2006.

Item 3 of the Research Plan of the R21 application may not exceed
6 pages, including tables,
graphs, figures, diagrams, and charts.

Introduction (required for a
resubmission application) is limited to one page.

Do not use the Appendix to circumvent the page limitations. An application that does not
observe the required page limitations may be delayed in the review process.

Foreign Applications (Non-Domestic
[non-U.S.] Entity)

Indicate how the proposed project
has specific relevance to the mission and objectives of the National Cancer
Institute and has the potential for significantly advancing the health sciences
in the United States.

Plan for Sharing
Research Data

NIH
policy expects that grant recipients make unique research resources readily available
for research purposes to qualified individuals within the scientific community
after publication (see the NIH Grants Policy Statement at http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131).
Investigators responding to this funding opportunity should include a sharing
research resources plan addressing how unique research resources will be shared
or explain why sharing is not possible.

The adequacy of the resources sharing plan and any
related data sharing plans will be considered by Program staff of the funding
organization when making recommendations about funding applications. The
effectiveness of the resource sharing will be evaluated as part of the
administrative review of each Non-Competing Grant
Progress Report (PHS 2590). See Section VI.3.,
Reporting.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be
considered in the review process.

2. Review and Selection
Process

Applications submitted for this funding opportunity will be assigned to
the ICs on the basis of established Public Health Services (PHS) referral
guidelines.

Applications that are complete will be evaluated for scientific and
technical merit by an appropriate peer review group convened by CSR and in
accordance with NIH peer review procedures
(http://grants1.nih.gov/grants/peer/), using the review criteria stated
below.

As part of the initial merit review, all applications
will:

Undergo a
selection process in which only those applications deemed to have the
highest scientific merit, generally the top half of applications under
review, will be discussed and assigned an impact/priority score;

Receive a
written critique; and

Receive a second level of review by the
National Cancer Advisory Board.

Applications submitted in
response to this funding opportunity will compete for available funds with all
other recommended applications. For a PAS, add "submitted in response to
this FOA." The following will be considered in making
funding decisions:

Scientific
and technical merit of the proposed project as determined by peer review.

Availability
of funds.

Relevance
of the proposed project to program priorities.

The NIH R21 exploratory/developmental grant is a
mechanism for supporting novel scientific ideas or new model systems, tools, or
technologies that have the potential to significantly advance our knowledge or
the status of health-related research.

Because the Research Strategy component is restricted to 6 pages, an
exploratory/developmental grant application need not have extensive
background material or preliminary information as one might normally expect
in an R01 application. Accordingly, reviewers will focus their evaluation on
the conceptual framework, the level of innovation, and the potential to
significantly advance our knowledge or understanding. Reviewers will place
less emphasis on methodological details and certain indicators traditionally
used in evaluating the scientific merit of R01 applications, including
supportive preliminary data. Appropriate justification for the proposed work
can be provided through literature citations, data from other sources, or,
when available, from investigator-generated data. Preliminary data are not
required for R21 applications; however, they may be included if available.

The mission of the NIH is to support science in pursuit
of knowledge about the biology and behavior of living systems and to apply
that knowledge to extend healthy life and reduce the burdens of illness and
disability. As part of this mission, applications submitted to the NIH for
grants or cooperative agreements to support biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH
peer review system.

Overall Impact. Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed).

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance: Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s): Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation: Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach: Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in
the early stages of development, will the strategy establish feasibility and
will particularly risky aspects be managed? Are the administrative plans for
the management of the research project appropriate, including plans for
resolving conflicts?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment: Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

2.A.
Additional Review Criteria

As applicable for the project
proposed, reviewers will consider the following additional items in the
determination of scientific and technical merit, but will not give separate
scores for these items.

Protections for Human Subjects. For
research that involves human subjects but does not involve one of the six
categories of research that are exempt under 45 CFR Part 46, the committee will
evaluate the justification for involvement of human subjects and the proposed
protections from research risk relating to their participation according to the
following five review criteria: 1) risk to subjects, 2) adequacy of protection
against risks, 3) potential benefits to the subjects and others, 4) importance
of the knowledge to be gained, and 5) data and safety monitoring for clinical
trials.

For research that involves human subjects and meets
the criteria for one or more of the six categories of research that are exempt
under 45 CFR Part 46, the committee will evaluate: 1) the justification for the
exemption, 2) human subjects involvement and characteristics, and 3) sources of
materials.

Inclusion of Women, Minorities, and Children.
When the proposed project involves clinical research, the committee will
evaluate the proposed plans for inclusion of minorities and members of both
genders, as well as the inclusion of children.

Vertebrate Animals. The committee
will evaluate the involvement of live vertebrate animals as part of the
scientific assessment according to the following five points: 1) proposed use of
the animals, and species, strains, ages, sex, and numbers to be used; 2)
justifications for the use of animals and for the appropriateness of the species
and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting
discomfort, distress, pain and injury to that which is unavoidable in the
conduct of scientifically sound research including the use of analgesic,
anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and
5) methods of euthanasia and reason for selection if not consistent with the
AVMA Guidelines on Euthanasia.

Resubmission Applications. When
reviewing a Resubmission application (formerly called an amended application),
the committee will evaluate the application as now presented, taking into
consideration the responses to comments from the previous scientific review
group and changes made to the project.

Renewal Applications. When reviewing
a Renewal application (formerly called a competing continuation application),
the committee will consider the progress made in the last funding period.

Revision Applications. When
reviewing a Revision application (formerly called a competing supplement
application), the committee will consider the appropriateness of the proposed
expansion of the scope of the project. If the Revision application relates to a
specific line of investigation presented in the original application that was
not recommended for approval by the committee, then the committee will consider
whether the responses to comments from the previous scientific review group are
adequate and whether substantial changes are clearly evident.

Biohazards. Reviewers will assess
whether materials or procedures proposed are potentially hazardous to research
personnel and/or the environment, and if needed, determine whether adequate
protection is proposed.

2.B Additional Review Considerations

As applicable for the project proposed, reviewers will
address each of the following items, but will not give scores for these items
and should not consider them in providing an overall impact/priority score.

Budget and Period Support. Reviewers will
consider whether the budget and the requested period of support are fully
justified and reasonable in relation to the proposed research.

Select Agent Research. Reviewers will
assess the information provided in this section of the application, including 1)
the Select Agent(s) to be used in the proposed research, 2) the registration
status of all entities where Select Agent(s) will be used, 3) the procedures
that will be used to monitor possession use and transfer of Select Agent(s), and
4) plans for appropriate biosafety, biocontainment, and security of the Select
Agent(s).

Applications from Foreign Organizations.
Reviewers will assess whether the project presents special opportunities for
furthering research programs through the use of unusual talent, resources,
populations, or environmental conditions that exist in other countries and
either are not readily available in the United States or augment existing U.S.
resources.

A formal notification in the form of a Notice of Award
(NoA) will be provided to the applicant organization. The NoA signed by the
grants management officer is the authorizing document. Once all administrative
and programmatic issues have been resolved, the NoA will be generated via email
notification from the awarding component to the grantee business official.

Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See Section
IV.5., Funding Restrictions.

We encourage your inquiries
concerning this funding opportunity and welcome the opportunity to answer
questions from potential applicants. Inquiries may fall into three areas:
scientific/research, peer review, and financial or grants management issues:

Human Subjects Protection:Federal regulations (45 CFR 46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and others,
and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:Data and safety monitoring is required for all types
of clinical trials, including physiologic toxicity and dose-finding studies
(Phase I); efficacy studies (Phase II); and efficacy, effectiveness, and
comparative trials (Phase III). Monitoring should be commensurate with risk.
The establishment of data and safety monitoring boards (DSMBs) is required for
multi-site clinical trials involving interventions that entail potential risks
to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide
for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their
institutions, on issues related to institutional policies and local
institutional review board (IRB) rules, as well as local, State, and Federal
laws and regulations, including the Privacy Rule. Reviewers will consider the
data sharing plan but will not factor the plan into the determination of the
scientific merit or the impact/priority score.

Access to Research Data through
the Freedom of Information Act:The Office of Management and Budget (OMB) Circular
A-110 has been revised to provide access to research data through the Freedom
of Information Act (FOIA) under some circumstances. Data that are: (1) first
produced in a project that is supported in whole or in part with Federal funds;
and (2) cited publicly and officially by a Federal agency in support of an
action that has the force and effect of law (i.e., a regulation) may be
accessed through FOIA. It is important for applicants to understand the basic
scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this funding opportunity in a
public archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the application.
In addition, applicants should think about how to structure informed consent
statements and other human subjects procedures given the potential for wider
use of data collected under this award.

Sharing of Model Organisms:NIH is committed to support efforts that encourage
sharing of important research resources including the sharing of model
organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time, the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding
pursuant to the Bayh-Dole Act (see the NIH
Grants Policy Statement). Beginning October 1, 2004, all investigators
submitting an NIH application or contract proposal are expected to include in
the application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.

Inclusion of Women, Minorities, and Children:It is the policy of the NIH that women and members of
minority groups and their sub-populations must be included in all NIH-supported
clinical research projects unless a clear and compelling justification is
provided indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results from the
NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All
investigators proposing clinical research should read the "NIH Guidelines
for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the SF424 (R&R) application; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a) all
applications or proposals and/or protocols must provide a description of plans
to conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting analyses,
as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical
Research:The NIH maintains a policy that children (i.e.,
individuals under the age of 21) must be included in all clinical research,
conducted or supported by the NIH, unless there are scientific and ethical
reasons not to include them.

Required Education on the Protection of Human
Subject Participants:NIH policy requires education on the protection of
human subject participants for all investigators submitting NIH applications
for research involving human subjects and individuals designated as key
personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):Criteria for federal funding of research on hESCs can
be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-116.html.
Only research using hESC lines that are registered in the NIH Human Embryonic
Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility
of the applicant to provide in the project description and elsewhere in the
application as appropriate, the official NIH identifier(s) for the hESC line(s)
to be used in the proposed research. Applications that do not provide this
information will be returned without review.

NIH Public Access Policy:NIH-funded investigators are requested to submit to
the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov)
at PubMed Central (PMC) an electronic version of the author's final manuscript
upon acceptance for publication, resulting from research supported in whole or
in part with direct costs from NIH. The author's final manuscript is defined
as the final version accepted for journal publication, and includes all
modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts
resulting from: 1) currently funded NIH research projects; or 2) previously
supported NIH research projects if they are accepted for publication on or
after May 2, 2005. The NIH Public Access Policy applies to all research grant
and career development award mechanisms, cooperative agreements, contracts,
Institutional and Individual Ruth L. Kirschstein National Research Service
Awards, as well as NIH intramural research studies. The Policy applies to
peer-reviewed, original research publications that have been supported in whole
or in part with direct costs from NIH, but it does not apply to book chapters,
editorials, reviews, or conference proceedings. Publications resulting from
non-NIH-supported research projects should not be submitted.

For more information about the Policy or the
submission process, please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view
the Policy or other Resources and Tools, including the Authors' Manual.

Standards for Privacy of Individually Identifiable
Health Information:The Department of Health and Human Services (HHS)
issued final modification to the "Standards for Privacy of Individually
Identifiable Health Information," the "Privacy Rule," on August
14, 2002. The Privacy Rule is a federal regulation under the Health Insurance
Portability and Accountability Act (HIPAA) of 1996 that governs the protection
of individually identifiable health information, and is administered and
enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of
the Privacy Rule reside with the researcher and his/her institution. The OCR
website (http://www.hhs.gov/ocr/)
provides information on the Privacy Rule, including a complete Regulation Text
and a set of decision tools on "Am I a covered entity?" Information
on the impact of the HIPAA Privacy Rule on NIH processes involving the review,
funding, and progress monitoring of grants, cooperative agreements, and
research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within
specified page limitations. For publications listed in the appendix and/or Progress
report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide
any other information necessary for the review because reviewers are
under no obligation to view the Internet sites. Furthermore, we caution
reviewers that their anonymity may be compromised when they directly access an
Internet site.

Healthy People
2010:The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of
"Healthy People 2010," a PHS-led national activity for setting
priority areas. This FOA is related to one or more of the priority areas.
Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:This program is described in the Catalog of Federal Domestic Assistance and is not subject to the intergovernmental review
requirements of Executive Order 12372 or Health Systems Agency review. Awards
are made under the authorization of Sections 301 and 405 of the Public Health
Service Act as amended (42 USC 241 and 284) and under
Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are
subject to the terms and conditions, cost principles, and other considerations
described in the NIH
Grants Policy Statement.

The PHS strongly encourages all grant recipients to
provide a smoke-free workplace and discourage the use of all tobacco products.
In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits
smoking in certain facilities (or in some cases, any portion of a facility) in
which regular or routine education, library, day care, health care, or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.

Loan Repayment Programs:NIH encourages applications for educational loan
repayment from qualified health professionals who have made a commitment to
pursue a research career involving clinical, pediatric, contraception,
infertility, and health disparities related areas. The LRP is an important
component of NIH's efforts to recruit and retain the next generation of
researchers by providing the means for developing a research career unfettered
by the burden of student loan debt. Note that an NIH grant is not required for
eligibility and concurrent career award and LRP applications are encouraged.
The periods of career award and LRP award may overlap providing the LRP
recipient with the required commitment of time and effort, as LRP awardees must
commit at least 50% of their time (at least 20 hours per week based on a 40
hour week) for 2 years to the research. For further information, please see http://www.lrp.nih.gov.